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Nanotechnology learns tricks from life

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By Alexandra Witze / The Dallas Morning News

The revolution of the future has been around for more than 3 billion years.

Human engineers are just now learning to build with atoms; biology has been doing it since life began. Every living thing works because its parts come together seamlessly in the ultratiny realm known as the nanoworld.

Living cells are nano-sized assembly lines of motors, clamps and probes that build and operate everything from sand fleas to giant sequoias.

"As you begin to understand what nature's doing, it's absolutely incredible," says Richard Smalley, a Nobel laureate and chemist at Rice University in Houston. "You can get so impressed with it that you get the feeling you can do anything."

Yet nature has its limits. It can put cells together to make a pumpkin. But it can't turn on spooky lights and play the "Monster Mash."

So biologists are marrying their expertise with that of chemists and physicists. Materials like metals and semiconductors, which usually live in the bowels of electronic machines, are being mated to the squirmy guts of cells.

But today's Dr. Frankensteins need a very small platform on which to weld the animate and inanimate. Individual cells measure just 1,000 to 10,000 nanometers, or billionths of a meter, across. And the cells are colossal compared with the molecules they are being mated with.

Revolution's prelude

The first results of these pairings are just now emerging from scientific laboratories.

At one university, a flailing enzyme whips its tail to crank a tiny motor. Elsewhere, DNA, the stuff of genetic inheritance, does double duty as a pair of grasping tweezers. Other researchers look to the abalone shell to inspire designs for materials that are many times stronger than steel.

In the next few decades, many scientists believe, this rendezvous between biology and traditional technology may yield great breakthroughs.

"This is very exciting, because you don't know what's going to work," says Barbara Baird, a biologist at Cornell University in Ithaca, N.Y. "The only way we're going to find out is try stuff."

And so the scientists play.

Many begin with DNA because it is the Forrest Gump of molecules – it shows up in so many important places. In its day job, deoxyribonucleic acid stores the molecular code for making all living things. But as if that job weren't enough, DNA also moonlights as a research tool in chemistry labs.

Its twin strands of chemicals, wrapped around each other in a double helix, can peel apart like wrappings off the Mummy. The molecule can also bend and slither around tight corners. Scientists have exploited this flexibility, using DNA to:

•Track the speed at which individual molecules flow in a stream.

•Shepherd tiny particles in a microscopic corral.

•Force nano-sized metal wires and crystals to grow in patterns.

•Flip a tiny switch on and off.

•Grasp and move other molecules.

DNA seems the perfect tool for almost any nanojob. It can even work on itself.

In an Illinois laboratory, Chad Mirkin and his colleagues have invented a way to identify individual DNA molecules in a possibly cheaper and faster way for checking crime-scene forensics.

The scientists first make some artificial DNA, each with a different designer sequence of chemicals. Then they mix single strands of synthetic DNA with the DNA they want to study. The two kinds latch on to each other in a double-stranded embrace.

Researchers then scatter nano-sized gold particles into the mix, which grab onto each DNA pairing. The whole experiment is heated. At higher temperatures, the molecular bonds between most DNA pairs fall apart. Only the best-matched synthetic and real DNA strands stay together.

What's left is a collection of perfect DNA matches, each flagged with a microscopic gold particle.

The scientists then drop the experiment into photographic developing solution, which coats the gold particles with layer after layer of silver. By looking for big, silver-coated blobs in the mix, the scientists can find where the DNA is. The bigger the blob, the more DNA exists at that spot.

The technique works better and more cheaply than other methods for analyzing DNA, the Northwestern University team reported this fall in the journal Science.

One day, the scientists say, doctors might use the technique in their office to directly test a person for genetic mutations.

DNA as a stencil

Other professions are also interested in DNA's many talents. Some chemical manufacturers, including photographic companies, need to be able to precisely control materials that have delicate, nanoscale patterns. These industries hope DNA can help.

At the University of California, Berkeley, a team led by Paul Alivisatos has shown that this is possible. The researchers use DNA as a traffic cop, telling the metallic nanocrystals how to grow into elaborate designs.

"We use it because we can create arbitrary patterns of enormous complexity," Dr. Alivisatos says.

Eventually, he hopes to coax nanocrystals into designs like those on a computer chip – an elaborate architecture of crystals, precisely arranged in neat, intersecting lines.

"I'm not sure where that's going to go," he says.

But some of the nanocrystal work has more immediate applications. For instance, his group has tucked nanocrystals into a petri dish with mouse cells. The crystals glow with a fluorescent green color when they grab onto the cells. One day, such work could lead to better ways to mark diseased cells in a body, Dr. Alivisatos says.

Tapping life's energy

DNA isn't biology's only versatile molecule for performing nanotricks. Many other biological molecules are now hooking up with manmade surfaces.

At Cornell, Carlo Montemagno and co-workers have linked, to a metal surface, an enzyme that thrives in almost every living thing. Molecules of ATPase – the enzyme that produces fuel within cells – naturally spin their tails like a hyperactive pencil sharpener. Dr. Montemagno has harnessed that energy to drive a motor the size of a single molecule. (See large illustration on Page 1F.)

Dr. Montemagno attaches the enzyme to the surface by a protein "shaft." The motor can zip around at several revolutions per second, for nearly an hour. Eventually, the scientists want to use a chemical to signal the motor to switch on and off.

So the motor might rev up when a particular chemical swims into its environment. Or it could power nano-sized chemical machines.

Such miniature machines exploit not only tiny size, but also the nanoworld's version of strength.

At the University of Texas at Austin, chemist Angela Belcher is trying to build a better seashell through nanotechnology. She's inspired by the fact that ordinary minerals can become extraordinary depending on how their molecules are arranged.

Animals like abalone and black-lipped oysters can make perfect nanocrystals on their own. Give them some calcium carbonate, known in geology as aragonite, and they will use the nanocrystals to build unbelievably strong, overlapping layers of shell.

"Biology makes it 3,000 times tougher than geology makes it," Dr. Belcher says.

She wants to exploit this ability, but with a twist – using electronic or magnetic materials that usually don't appear in nature.

Her research team has coaxed naturally occurring chemicals, called peptides, to hook onto semiconducting nanocrystals. In some cases, the peptides will latch onto one particular surface of the crystal, the team reported this summer in Nature.

"All the potential applications are very long-term," Dr. Belcher says. But if scientists could consistently grow crystals the way they wanted them, where they wanted them, the discoveries could help develop better lasers, optics or electronics. Biological molecules could help shape miniature electronic devices by laying down wires or other parts of a circuit.

Learning from biology

Scientists will have an easier time working in the nanoworld if they can get the parts to assemble themselves naturally, Dr. Belcher says.

"We want to harness the potential that biology has already developed," she says.

In some cases, that calls for outsmarting the monstrous side of biology.

For instance, Cornell researchers have devised a tiny sensor to trap E. coli bacteria before they contaminate food supplies. Other teams work on sensors that might detect nerve gas or other toxins on the battlefield. Crafting the devices at the nanoscale might cut down on the number of false alarms, says Carl Batt, co-director of Cornell's Nanobiotechnology Center.

At the University of Michigan, Donald Tomalia and colleagues are using chemistry to fake out biology.

They've designed a set of tree-shaped molecules that act as miniature decoys against the influenza virus. The molecules display a surface that looks tempting to the virus, which latches on in an attempt to infect. But then the virus finds itself stuck on the molecule, unable to unlock itself.

These "nanodecoys" have been tested only in petri dishes, but they did prevent the virus from attaching to cells, the Michigan team reported at an American Chemical Society meeting this fall.

Someday, doctors hope nanotechnology might give them new gadgets to detect disease, deliver drugs into a person's body or even monitor how a patient is doing minute by minute. The National Institutes of Health, for example, is chipping in $36 million in a new federal push for nanotechnology research.

The marriage of biology and nanotechnology will undoubtedly produce offspring, scientists believe. But it's too soon to tell what their progeny might look like.

Scientists are learning as they go along, says Cornell's Dr. Baird.

"In a sense," she says, "we're all new at this."
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